7SEJ

Structure-based design of prefusion-stabilized human metapneumovirus fusion proteins

7SEJ の概要

• エントリーDOI: 10.2210/pdb7sej/pdb
• 分子名称: Fusion glycoprotein F2 subunit, Fusion glycoprotein F1 subunit, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: human metapneumovirus, fusion protein, viral protein
• 由来する生物種: Human metapneumovirus; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 121828.56

構造登録者

Hsieh, C.-L.,Rush, S.A.,McLellan, J.S. (登録日: 2021-09-30, 公開日: 2022-02-09, 最終更新日: 2024-10-23)

主引用文献

Hsieh, C.L.,Rush, S.A.,Palomo, C.,Chou, C.W.,Pickens, W.,Mas, V.,McLellan, J.S.
Structure-based design of prefusion-stabilized human metapneumovirus fusion proteins.
Nat Commun, 13:1299-1299, 2022

PubMed Abstract: The human metapneumovirus (hMPV) fusion (F) protein is essential for viral entry and is a key target of neutralizing antibodies and vaccine development. The prefusion conformation is thought to be the optimal vaccine antigen, but previously described prefusion F proteins expressed poorly and were not well stabilized. Here, we use structures of hMPV F to guide the design of 42 variants containing stabilizing substitutions. Through combinatorial addition of disulfide bonds, cavity-filling substitutions, and improved electrostatic interactions, we describe a prefusion-stabilized F protein (DS-CavEs2) that expresses at 15 mg/L and has a melting temperature of 71.9 °C. Crystal structures of two prefusion-stabilized hMPV F variants reveal that antigenic surfaces are largely unperturbed. Importantly, immunization of mice with DS-CavEs2 elicits significantly higher neutralizing antibody titers against hMPV A1 and B1 viruses than postfusion F. The improved properties of DS-CavEs2 will advance the development of hMPV vaccines and the isolation of therapeutic antibodies.

PubMed: 35288548
DOI: 10.1038/s41467-022-28931-3

実験手法

X-RAY DIFFRACTION (2.51 Å)